Spatial and Temporal Control of Molecular Interactions in Surfactant Systems

智能优点：这个项目是一项旨在利用还原活性表面活性剂和电化学方法来实现表面活性剂与DNA相互作用的空间和时间控制的研究。这项研究的动机是最近发表的研究人员的观察结果，即操纵二茂铁基表面活性剂的氧化态可以用来控制细胞的转染。研究的第一个目标是使用光散射和中子散射测量来确定DNA与含有氧化还原活性基团的二茂铁的表面活性剂的相互作用如何依赖于二茂铁的氧化态：二茂铁经历可逆单电子氧化，从电中性状态到带电(+1)状态。被研究的表面活性剂包含两个二茂铁基团，并在二茂铁氧化时经历电荷从(+1)到(+3)的变化。我们假设，二茂铁氧化状态的改变将导致表面活性剂与DNA之间的静电相互作用发生实质性的变化，从而改变这些物种形成的络合物的大小和微观结构。本研究的第二个目标是了解发生在含二茂铁表面活性剂水溶液中的电极附近的迁移和自组装过程。通过使用薄膜电化学池，研究人员将研究表面活性剂自组装过程的动力学影响，以及表面活性剂与添加的DNA之间的相互作用对电极100范围内溶液性质的影响。以上两项研究的结果结合在一起，将为实现对DNA和含二茂铁表面活性剂之间形成络合物的空间和时间控制提供原理。广泛影响：本建议中描述的研究将提供对氧化还原活性表面活性剂在电极上的氧化状态的空间局域变化如何影响其与DNA等生物分子的结合的理解。这些主题都是智力丰富的主题，将广泛地促进我们对表面活性剂和生物分子体系中的分子相互作用的理解。此外，它还讨论了表面活性剂体系中相对鲜为人知的动力学主题。如上所述，研究人员已经证明，二茂铁基表面活性剂的氧化状态可以对细胞的转染，即向细胞输送DNA产生显著影响。了解这些表面活性剂与DNA的相互作用，以及控制电极附近这些溶液性质局部变化的基本因素，将有助于进一步发展这些控制基因转移的新原理以及其他一些潜在的应用(蛋白质结晶、微尺度分离、介观材料合成)。这项研究通过结合胶体化学、界面工程(雅培)、生物分子和材料工程(LYN)和流体力学/质量传输现象(格雷厄姆)的项目，为正在进行的两名女研究生的教育提供了令人兴奋的机会。学生们将有机会体验以发现为导向的实验研究以及互补的数值建模和分析。由于削减了原来的预算，预期成果和范围都缩小到了整个项目的第一阶段。

ABSTRACTIntellectual Merit: This project is an investigation that aims to useredox-active surfactants and electrochemical methods to achieve spatial and temporalcontrol over the interactions of surfactants with DNA. The study is motivated by theinvestigators recently published observation that manipulation of the oxidation state offerrocenyl surfactants can be used to control transfection of cells.The first goal of the research is to use light scattering and neutron scattering measurements to determine how the interactions of DNA with surfactants containing the redox-active group ferrocene depend on the oxidation state of the ferrocene: ferrocene undergoes a reversible one electron oxidation from an electrically neutral state to a charged (+1) state. The surfactants to be studied incorporate two ferrocene groups and undergo a change in charge from (+1) to (+3) upon oxidation of the ferrocene. We hypothesize that changes in the oxidation state of the ferrocene will lead to substantial changes in electrostatic interactions between the surfactants and DNA and thus changes in the sizes and microstructures of complexes formed by these species.The second goal of the research described in this proposal is to understand thetransport and self-assembly processes that occur near electrodes immersed into aqueoussolutions of ferrocene-containing surfactants. By using a thin film electrochemical cell,the investigator will investigate the influence of the dynamics of surfactant self-assembly processes as well as the influence of interactions between the surfactants with added DNA on the properties of solutions within 100 of an electrode.The results of the above two studies, when combined, would provide principles for achieving spatial and temporal control over the formation of complexes between DNAand ferrocene-containing surfactants.Broader Impacts: The studies described in this proposal will provide understanding in how spatially localized changes in the oxidation states of redox-active surfactants at electrodes impact their association with biological molecules such as DNA. These topics are intellectually rich ones that will broadly advance our understanding of molecular interactions in surfactants and biomolecular systems. In addition, it addresses the relatively poorly understood topic of dynamics in surfactant systems. As describedabove, the investigators have already shown that the oxidation state of ferrocenylsurfactants can have a dramatic effect on the transfection of cells, i.e., the delivery of DNA to cells. Knowledge of the interactions of these surfactants with DNA, as well as knowledge of the fundamental factors that govern the generation of localized changes in the properties of these solutions near electrodes, will enable further development of these novel principles for control of transfection as well as a number of other potential applications (protein crystallization, microscale separations, meso-scale materials synthesis). The research provides exciting opportunities for ongoing the education of two female graduate students through projects that combine colloid chemistry, interface engineering (Abbott), biomolecular and materials engineering (Lynn) and fluid mechanics/mass transport phenomena (Graham). The students will be presented with the unusual opportunity of being able to experience both discovery oriented experimental research as well as complementary numerical modeling and analysis. Because of the reduction of the original budget, the expected results and scope have been reduced to the first stages of the overall project.